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121.
Nguyen TV Ke Y Zhang EE Feng GS 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(9):5990-5996
It is well known that T cell differentiation and maturation in the thymus is tightly controlled at multiple checkpoints. However, the molecular mechanism for the control of this developmental program is not fully understood. A number of protein tyrosine kinases, such as Zap-70, Lck, and Fyn, have been shown to promote signals required for thymocyte development, whereas a tyrosine phosphatase Src homology domain-containing tyrosine phosphatase (Shp)1 has a negative effect in pre-TCR and TCR signaling. We show in this study that Shp2, a close relative of Shp1, plays a positive role in T cell development and functions. Lck-Cre-mediated deletion of Shp2 in the thymus resulted in a significant block in thymocyte differentiation/proliferation instructed by the pre-TCR at the beta selection step, and reduced expansion of CD4(+) T cells. Furthermore, mature Shp2(-/-) T cells showed decreased TCR signaling in vitro. Mechanistically, Shp2 acts to promote TCR signaling through the ERK pathway, with impaired activation of ERK kinase observed in Shp2(-/-) T cells. Thus, our results provide physiological evidence that Shp2 is a common signal transducer for pre-TCR and TCR in promoting T cell maturation and proliferation. 相似文献
122.
Jean Frantz Lemoine Anne Marie Desormeaux Franck Monestime Carl Renad Fayette Luccene Desir Abdel Nasser Direny Sarah Carciunoiu Lior Miller Alaine Knipes Patrick Lammie Penelope Smith Melissa Stockton Lily Trofimovich Kalpana Bhandari Richard Reithinger Kathryn Crowley Eric Ottesen Margaret Baker 《PLoS neglected tropical diseases》2016,10(10)
Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti’s neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a “directly observed treatment” strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained– 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH—and the significant reduction in burden of infection– 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti’s very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of “best practices” for NTD control but also are poised to help solve two of the most important future NTD challenges—how to maintain control of STH infections after the community-based LF “treatment platform” ceases and how to ensure appropriate morbidity management for patients currently suffering from lymphatic filarial disease. 相似文献
123.
Britta Gribsholt Eric Struyf Anton Tramper Maria G. I. Andersson Natacha Brion Loreto De Brabandere Stefan Van Damme Patrick Meire Jack J. Middelburg Frank Dehairs Henricus T. S. Boschker 《Biogeochemistry》2006,80(3):289-298
The fate and transport of watershed-derived ammonium in a tidal freshwater marsh fringing the nutrient rich Scheldt River,
Belgium, was quantified in a whole ecosystem 15N labeling experiment. In late summer (September) we added 15N-NH4+ to the flood water entering a 3477 m2 tidal freshwater marsh area, and traced the ammonium processing and retention in four subsequent tide cycles. In this paper
we present the results for the water-phase components of the marsh system and compare them to a similar experiment conducted
in spring/early summer (May). Changes in concentration and isotopic enrichment of NO3− + NO2−, N2O, N2, NH4+ and suspended particulate nitrogen (SPN) were measured in concert with a mass balance study. All analyzed N-pools were labeled,
and 49% of the added 15NH4+ was retained or transformed. The most important pool for 15N was nitrate, accounting for 17% of 15N-transformation. N2, N2O and SPN accounted for 2.4, 0.02 and 1.4%, respectively. The temporal and spatial patterns of 15N transformation in the water phase component of the system were remarkably similar to those observed in May, indicating good
reproducibility of the whole ecosystem labeling approach, but the absolute ammonium transformation rate was 3 times higher
in May. While the marsh surface area was crucial for nitrification in May this was less pronounced in September. Denitrification,
on the other hand, appeared more important in September compared to May. 相似文献
124.
Sherita Hill Golden Wendy L. Bennett Kesha Baptist-Roberts Lisa M. Wilson Bethany Barone Tiffany L. Gary Eric Bass Wanda K. Nicholson 《Gender Medicine》2009
Background: Women with a history of gestational diabetes mellitus (GDM) are at high risk for type 2 diabetes mellitus (T2DM).Objective: We reviewed prospective studies of antepartum glucose tolerance test results as risk factors for development of T2DM among women with a history of GDM.Methods: We searched 4 electronic databases and hand-searched 13 journals for literature published through January 2007. The search strategy consisted of medical subject headings and text words for GDM, T2DM, and other relevant terms. Articles were excluded for the following reasons: (1) not written in English; (2) no human data; (3) no original data; (4) <90% of sample was diagnosed with GDM without a separate analysis for women with GDM; (5) case report or series; (6) diagnosis of GDM not based on 3-hour 100-g oral glucose tolerance test (OGTT) or 2-hour 75-g OGTT; (7) T2DM not evaluated as outcome; (8) no relative measure of association or incidence reported; or (9) design did not address antepartum OGTT as a predictor of T2DM. Two investigators independently reviewed citations, performed serial data abstraction on full articles, and assessed the quality of each article. Data were abstracted for study participants and characteristics, T2DM diagnosis, length of follow-up, regression model covariates, and measures of association and variability.Results: Of 11,400 unique citations, we identified 11 articles that evaluated antepartum glucose testing and risk of T2DM in women with a history of GDM. Five studies found that the fasting blood glucose (FBG) on the antepartum diagnostic OGTT was a significant predictor of T2DM (odds ratio [OR] range: 11.1–21.0; relative risk [RR] range: 1.37–1.5; relative hazard [RH] = 2.47). Risk of incident T2DM was predicted by the antepartum 2-hour OGTT plasma glucose in 3 studies (OR range: 1.02–1.03; RR = 1.3) and by the antepartum OGTT glucose AUC in 3 other studies (OR range: 3.64–15; RH = 2.13). Overall, study quality was limited by high losses to follow-up (>20% in 6 studies) and short duration. Few studies adjusted for adiposity, an established diabetes risk factor.Conclusion: FBG, OGTT 2-hour blood glucose, and OGTT glucose AUC appeared to be strong and consistent predictors of subsequent T2DM among women who met diagnostic criteria for GDM using the OGTT. 相似文献
125.
Pragl B Koschak A Trieb M Obermair G Kaufmann WA Gerster U Blanc E Hahn C Prinz H Schütz G Darbon H Gruber HJ Knaus HG 《Bioconjugate chemistry》2002,13(3):416-425
Hongotoxin(1) (HgTX(1)), a 39-residue peptide recently isolated from the venom of Centruroides limbatus, blocks the voltage-gated K+ channels K(v)1.1, K(v)1.2, and K(v)1.3 at picomolar toxin concentrations (Koschak, A., Bugianesi, R. M., Mitterdorfer, J., Kaczorowski, G. J., Garcia, M. L., and Knaus, H. G. (1998) J. Biol. Chem. 273, 2639-2644). In this report, we determine the three-dimensional structure of HgTX(1) using NMR spectroscopy (PDB-code: 1HLY). HgTX(1) was found to possess a structure similar to previously characterized K+ channel toxins (e.g. margatoxin) consisting of a three-stranded antiparallel beta-sheet (residues 2-4, 26-30, and 33-37) and a helical conformation (part 3(10) helix and part alpha helix; residues 10-20). Due to the importance of residue Lys-28 for high-affinity interaction with the respective channels, lysine-reactive fluorescence dyes cannot be used to label wild-type HgTX(1). On the basis of previous studies (see above) and our NMR data, a HgTX(1) mutant (HgTX(1)-A19C) was engineered, expressed, and purified. HgTX(1)-A19C-SH was labeled using sulfhydryl-reactive Cy3-, Cy5-, and Alexa-dyes. Pharmacological characterization of fluorescently labeled HgTX(1)-A19C in radioligand binding studies indicated that these hongotoxin(1) analogues retain high-affinity for voltage-gated K+ channels and a respective pharmacological profile. Cy3- and Alexa-dye-labeled hongotoxin(1) analogues were used to investigate the localization of K+ channels in brain sections. The distribution of toxin binding closely follows the distribution of K(v)1.2 immunoreactivity with the highest expression levels in the cerebellar Purkinje cell layer. Taken together, these results demonstrate that fluorescently labeled HgTX(1) analogues comprise novel probes to characterize a subset of voltage-gated K+ channels. 相似文献
126.
Karmella A Haynes Marian L Broderick Adam D Brown Trevor L Butner James O Dickson W Lance Harden Lane H Heard Eric L Jessen Kelly J Malloy Brad J Ogden Sabriya Rosemond Samantha Simpson Erin Zwack A Malcolm Campbell Todd T Eckdahl Laurie J Heyer Jeffrey L Poet 《Journal of biological engineering》2008,2(1):1-12
127.
Interactions with humans impact many aspects of behavior and ecology in nonhuman primates. Because of the complexities of
the human–nonhuman primate interface, methods are needed to quantify the effects of anthropogenic interactions, including
their intensity and differential impacts between nonhuman primate groups. Stable isotopes can be used to quickly and economically
assess intergroup dietary variation, and provide a framework for the development of specific hypotheses about anthropogenic
impact. This study uses stable carbon and nitrogen isotope analysis to examine intraspecific variation in diet between five
groups of Barbary macaques, Macaca sylvanus, in the Upper Rock Nature Reserve, Gibraltar. Analysis of hair from 135 macaques showed significant differences in δ13C and δ15N values between a group with minimal tourist contact and groups that were main tourist attractions. Because we observed no
overt physiological or substantial behavioral differences between the groups, feeding ecology is the most likely cause of
any differences in stable isotope ratios. Haphazard provisioning by tourists and Gibraltarians is a likely source of dietary
variation between groups. Stable isotope analysis and observational data facilitate a deeper understanding of the feeding
ecology of the Barbary macaques relevant to the role of an anthropogenic ecology for the species. 相似文献
128.
Gilman Eric Chaloupka Milani Ishizaki Asuka Carnes Mathew Naholowaa Hollyann Brady Colby Ellgen Sarah Kingma Eric 《Reviews in Fish Biology and Fisheries》2021,31(3):653-666
Reviews in Fish Biology and Fisheries - Albatross bycatch has been increasing over the past decade in the US tuna longline fishery of the central North Pacific. A controlled field... 相似文献
129.
Herein we report on the semisynthesis and biological evaluation of β-amino alcohol derivatives of the natural product totarol and other simple aromatic systems. All β-amino alcohol derivatives of totarol exhibited higher antiplasmodial activity than totarol [IC(50): 11.69 μM (K1, chloroquine and multi-drug resistant strain), and 11.78 μM (D10, chloroquine sensitive strain)]-12e was the most active [IC(50): 0.63 μM (K1), and 0.61 μM (D10)]. The phenyl and naphthyl β-amino alcohol derivatives were much less active than their corresponding totarol equivalents. The majority of the β-amino alcohol derivatives of totarol were more active against K1 than the D10 strains of Plasmodium falciparum, a trend similar to the inverse relationship observed with the established aryl-amino alcohol antimalarial mefloquine. Selected compounds were shown to affect erythrocyte morphology, inhibit erythrocyte invasion and trigger CQ accumulation. 相似文献
130.
Christopher S. Bland Eric T. Wang Anthony Vu Marjorie P. David John C. Castle Jason M. Johnson Christopher B. Burge Thomas A. Cooper 《Nucleic acids research》2010,38(21):7651-7664
Recent genome-wide analyses have elucidated the extent of alternative splicing (AS) in mammals, often focusing on comparisons of splice isoforms between differentiated tissues. However, regulated splicing changes are likely to be important in biological transitions such as cellular differentiation, or response to environmental stimuli. To assess the extent and significance of AS in myogenesis, we used splicing-sensitive microarray analysis of differentiating C2C12 myoblasts. We identified 95 AS events that undergo robust splicing transitions during C2C12 differentiation. More than half of the splicing transitions are conserved during differentiation of avian myoblasts, suggesting the products and timing of transitions are functionally significant. The majority of splicing transitions during C2C12 differentiation fall into four temporal patterns and were dependent on the myogenic program, suggesting that they are integral components of myogenic differentiation. Computational analyses revealed enrichment of many sequence motifs within the upstream and downstream intronic regions near the alternatively spliced regions corresponding to binding sites of splicing regulators. Western analyses demonstrated that several splicing regulators undergo dynamic changes in nuclear abundance during differentiation. These findings show that within a developmental context, AS is a highly regulated and conserved process, suggesting a major role for AS regulation in myogenic differentiation. 相似文献